Chronic Lymphocytic Leukemia, T-Cell Large Granular Lymphocytic Leukemia in a Pediatric Patient without Underlying Condition

Background Large granular lymphocytic (LGL) leukemia is a rare hematological malignancy in children. The two types of LGL leukemia that have been described are T-cell and Natural Killer cell leukemia. It is most commonly diagnosed in older adults, average age of 60-year-old. About 20 cases of LGL leukemia have been reported in children and young adults. All the patients in the reported cases had immune dysregulation conditions, such as chronic graft versus host disease, common variable immunodeficiency disorder, Crohn's disease and autoimmune hemolytic anemia. Here we report a case of T-cell LGL leukemia in a 11-year-old boy without underlying condition who presented with chronic neutropenia associated with gingival hypertrophy, recurrent skin abscesses, aphthous ulcers, clubbing of nails and low bone density. Methods Multi-institution collaboration and literature review. Case Description 11-year-old male with two years history of episodic gum bleeding with gingival hypertrophy, skin abscesses, aphthous ulcers, chronic neutropenia and lymphocytosis presented to our clinic for further evaluation. Initial workup demonstrated moderate to severe neutropenia (absolute neutrophil count between 400/ul to 800/ul) with low segmented neutrophils of 2-4% and high lymphocytes of more than 80%, but normal white blood cell count, hemoglobin for age and platelet count. Peripheral blood smear showed several variant lymphocytes with cytoplasmic blebs and no immature cells present. Expansion of T-cell large granular lymphocytes were detected in peripheral blood by flow cytometry. Due to new symptom of lower back pain, a lumbar Magnetic Resonance Imaging was performed. Results showed low bone density with mild compression deformity of L1 and abnormal heterogeneous marrow signal with heterogeneous contrast enhancement. The abnormal bone marrow signal promoted the investigation of bone marrow aspiration and biopsy. Flow cytometry detected forty-five percent of lymphocytes with immuno-phenotype of CD3+, CD8+, CD57+, CD16+, CD7+ and CD5-. The morphology of minimal cytoplasm and mature chromatin along with immunophenotype were consistent with clonal T-cell large granular lymphocytic proliferation/leukemia. Further cytogenetic tests showed TCR gamma and beta genes rearrangement, STAT3 N647I mutation with normal male karyotype. A peripheral blood congenital neutropenia panel, which included a total of 18 genes, found a heterozygous mutation c 279 G>A in the Gata2 gene; a variant of uncertain significance. Next generation sequencing showed somatic mutations of TRGV10, TRGV8 TRGJ1, TNFAIP3 and STAT3. However, there was no germline mutations detected in sample from skin biopsy. Comprehensive evaluation by immunology, rheumatology and gastroenterology failed to detect any underlying conditions. Conclusion Due to rarity of LGL leukemia in pediatrics, standard of care guidelines are currently unavailable. Extrapolated from limited literature, two management options are considered: watch and wait approach versus early initiation of immunosuppressant chemotherapy. Improved diagnostics can aide management strategies in this patient population. Disclosures No relevant conflicts of interest to declare.

Dental implants: a potential cause of bone marrow edema in the jaw—preliminary report

Background Different magnetic resonance imaging (MRI) sequences are frequently used to examine bone marrow in the jaw, including short tau inversion recovery (STIR). MRI is a sensitive method for detecting bone marrow lesions. Currently, pantomography and computed tomography (CT) are used frequently for preoperative dental implant treatment. However, no study has evaluated bone marrow edema around dental implants using MRI. This study aimed to assess bone marrow edema in the jaw around dental implants using brain magnetic resonance images. Methods This retrospective cohort study was approved by our university ethics committee (EC19-011). A total of 17 patients (170 sites) who underwent brain MRI between April 2010 and March 2016 were analyzed. All subjects underwent scanning more than 3 years after implant placement. This study investigated two bone marrow signals (with implant site and without implant site). These two groups were then compared using Fisher’s exact test. The Mann–Whitney U test was used to analyze bone marrow signal intensity as the dependent variable and the long and short-axis diameters of the implant as the independent variables. Results The were 22/31 sites (71%) and 38/139 sites (27%) of bone marrow edema in the dental implants and without dental implants groups, respectively (p < 0.001). Furthermore, there was a significant correlation between bone marrow signal intensity and the short-axis diameter of the implant (p < 0.001). Conclusion The signal intensity in the bone marrow sites in the jaw with dental implants was significantly higher than that in the sites without dental implants. The present study findings suggest that dental implants are a potential cause of bone marrow edema in the jaw.

The Prediction of Lymphohematopoietic Diseases by Incidentally-Detected Diffuse Signal Alterations of Bone Marrow on MRI

Objective: Advanced imaging techniques are increasingly used in the diagnostic workup of patients. The clinical significance of incidentally-detected signal alterations of the bone marrow on magnetic resonance imaging has not been widely studied. The purpose of this study was to determine whether bone marrow signal changing on magnetic resonance imaging could predict a hematologic disease. Materials and Methods: Thirty patients who were referred to Hematology department due to bone marrow signal alteration on magnetic resonance imaging between the years of 2011 and 2018 were evaluated. Results: There were 8 males and 22 females with a median age of 53 (range, 31–86) years at the time of presentation to the Hematology clinic. The magnetic resonance imaging studies had been taken because the patients had complaints of pain in extremities or lumbago (80%). The patients had been followed for median 4.5 months (0-71.7). Six (20%) cases had a bone marrow biopsy at presentation and a diagnosis was established in 5 (16.6%) of them (1 patient was diagnosed acute myeloid leukemia, 4 patients were diagnosed multiple myeloma). Marrow biopsy was done in 11 of the cases during follow-up median 3.8 months (1.3-11.5) after presentation. A diagnosis was made in 9 cases (5 patients were diagnosed multiple myeloma, 2 patients were diagnosed follicular lymphoma, 1 patient was diagnosed waldenstrom macroglobulinemia). Thirteen cases never had a biopsy. These cases had been followed for 1.3 months (0-71.7). None of them showed clinical abnormalities related to a lymphohematopoietic disorder and/or diagnosed with such a disorder. Only 1 patient was diagnosed with osteomalacia at follow-up. Conclusion: Incidentally-detected signal alterations of the bone marrow on magnetic resonance imaging should trigger investigations for a marrow problem. Most of the diagnosis patients were multiple myeloma. Extremity pain and findings like anemia may be associated with lymphohematological malignancies.

Edema-like marrow signal intensity: a narrative review with a pictorial essay

The term edema-like marrow signal intensity (ELMSI) represents a general term describing an area of abnormal signal intensity at MRI. Its appearance includes absence of clear margins and the possibility of exceeding well-defined anatomical borders (for example, physeal scars). We can define “ELMSI with unknown cause” an entity where the characteristic MR appearance is associated with the absence of specific signs of an underlying condition. However, it is more often an important finding indicating the presence of an underlying disease, and we describe this case as “ELMSI with known cause.” It presents a dynamic behavior and its evolution can largely vary. It initially corresponds to an acute inflammatory response with edema, before being variably replaced by more permanent marrow remodeling changes such as fibrosis or myxomatous connective tissue that can occur over time. It is important to study ELMSI variations over time in order to evaluate the activity state and therapeutic response of an inflammatory chronic joint disease, the resolution of a trauma, and the severity of an osteoarthritis. We propose a narrative review of the literature dealing with various subjects about this challenging topic that is imaging, temporal evolution, etiology, differential diagnoses, and possible organization, together with a pictorial essay.

THU0518 ACCURACY OF DUAL-ENERGY COMPUTED TOMOGRAPHY FOR THE DETECTION OF BONE MARROW EDEMA IN PATIENTS WITH AXIAL SPONDYLOARTHRITIS

Background:An important applications of the Dual energy computed tomography DECT in the field of musculoskeletal radiology is the detection of bone marrow edema (BME), using a post-processing software to remove calcium in trabecular bone by using a “virtual non-calcium (VNCa)” subtraction process DECT have been successfully employed in the evaluation of the extent of BME in patients with sacroiliitis (1)Objectives:The aims of this study were i)to evaluate the discriminating capacity of DECT versus MRI in the detection of BME of the sacroiliac joints in patients with axial-SpA and to define the optimal cutoff; ii) to define of inter-observer agreement between radiologistsMethods:All patients underwent a pelvic DECT examination, within 30 days of the MRI imaging, (Somatom Force; Siemens Healthineers, Enlangen, Germany). Each exam was evaluated by two operators: an experienced radiologist and a radiologist in training. The dedicated software also allows the precise calculation of the attenuation values in the region of interest (ROI). On the reformatted color-coded dual-energy virtual non-calcium images bone marrow signal is depicted in green and corresponding to high signal intensity on T2-weighted fat suppression MR images (Fig. 1). With the consent of the two operators, three ROIs were manually positioned for each side of the sacroiliac joints in the subchondral region of the proximal, middle and distal thirds of each joint head, respectively. The interobserver agreement analysis was carried out in the semi-quantitative evaluation of the scores assigned in CT. The accuracy of DECT for the detection of BME compared to MRI was analyzed using the Receiver Operating Characteristics (ROC) curve methodFigure 1.Patient with SpA A. Short tau inversion recovery MR image demonstrating extensive BME in both iliac and sacral subchondral bone, indicating active sacroiliitis. B. CT Semicoronal multiplanar reformatted grayscale image shows signs of structural change. C. Semicoronal multiplanar reformatted color-coded dual-energyVNCaimage reveals bone marrow signal involving both sacroliliac joints, corresponds toBMEon the MR imageResults:56 axial-SpA patients have been evaluated, 30 males and 26 females, a mean age of 48.6 ± 12.3 years, a mean disease duration of 5.5 ± 2.9 years, a mean C-reactive protein level of 3.0 ± 2.5 mg/dl. The inter-rater agreement of readers showed a high statistical significance greater than 0.80, in particular the weighted kappa is 0.815, with a standard error of 0.04 and a 95% variability coefficient between 0.73 and 0.89. Sensitivity, specificity, and positive likelihood ratio in the identification of BME at DECT were 95.8%, 83.3% and 6.67, respectively. The differences in mean CT number (HU) among the four levels of edema category were significant (p<0.0001). The AUC was 0.905 in the differentiation of the presence of BME from no edema (Fig. 2). A cutoff value of –14.8 HU yielded overall sensitivity of 82.86% and specificity of 90.48%, with an LR+ of 8.70, in the detection of BMEFigure 2.Graph shows ROC curves from CT numbers (in Hounsfield units) derived from DECT images in the detection of sacroiliitis with and without BME. AUC was 0.905Conclusion:We confirm the potential of DECT for the detection of BME of the sacroiliac joints in patients affected by SpA. This new method appears to be very useful, not only in the diagnostic phase, but also for the monitoring of patients.References:[1]Carotti M, Salaffi F, Beci G, Giovagnoni A. The application of dual-energy computed tomography in the diagnosis of musculoskeletal disorders: a review of current concepts and applications. Radiol Med. 2019;124(11):1175-1183.Disclosure of Interests:None declared